Studying schizophrenia in vitro
15 Jun 2011 by Evoluted New Media
After a century of examination, the cause of schizophrenia remains unknown, but a group of American scientists believe they’ve moved a step closer to understanding the diseases biological underpinnings.
After a century of examination, the cause of schizophrenia remains unknown, but a group of American scientists believe they’ve moved a step closer to understanding the diseases biological underpinnings.
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American scientists study underlying causes of schizophrenia in vitro |
Researchers from the Salk Institute for Biological Studies used induced pluripotent stem cells (iPCS) generated from schizophrenic patients and a modified rabies virus to discover just what goes on in the brain of schizophrenics. It turns out; schizophrenic neurons make fewer connections to each other, and have fewer projections growing from their cells bodies.
“This is the first time that a complex mental disease has been modelled in live human cells,” said Fred Gage, professor of genetics. “This model not only affords us the opportunity to look at live neurons from schizophrenia patients and healthy individuals to understand more about the disease mechanism, but also to screen for drugs that may be effective in reversing it.”
Postdoctoral researcher Kristen Brennand reprogrammed into iPCSs skin fibroblasts from four schizophrenia patients with a hereditary history of the disease, and differentiated these into neurons. A modified rabies virus enables her to highlight the connections between neurons and detect differences between normal neurons and those originating from schizophrenia patients.
“It was really reassuring that in most ways, these ‘schizophrenic’ neurons are in fact indistinguishable from normal ones,” she said.
The viral tracer showed that the schizophrenic neurons connected less frequently with each other, and had fewer projections growing out of their cell bodies. Gene expression profiles also identified 600 genes whose activity was misregulated in these neurons – 25% of which had previously been implicated.
Brennand also administered a number of frequently prescribed antipsychotic medications for the final three weeks of neuronal differentiation to test their ability to improve connectivity in vitro. Only Loxapine – which acts on dopamine receptors in the brain – increased neurons’ ability to connect with their neighbours.
“These drugs are doing a lot more than we thought they were doing,” Brennand said. “But now, for the very first time, we have a model system that allows us to study how antipsychotic drugs work in live, genetically identical neurons from patients with known clinical outcomes, and we can start correlating pharmacological effects with symptoms.”
